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Comorbidity of mental disorders and substance use: a brief guide for the primary care clinician

10.5 Major clinical issues with somatoform disorders and opioid use

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• Emphasis should always be placed on non-medication management of the somatoform disorder as a first line of treatment.
• CBT has shown reductions in somatic symptoms and improved functioning in people with somatoform disorders.
• The patient should be managed with the assistance of a clinical psychologist with experience in the management of pain.
• If exercise and rehabilitation avoidance behaviours are present, then the help of a physiotherapist with experience in the area will be required.
• People with somatoform and pain disorders frequently use opioids. Due to the chronic nature of the pain and subsequent opioid use, dependence is common.
• However, long-term opioid use can result not only in tolerance but can actually cause pain hypersensitivity, potentially exacerbating somatic symptoms.
• Methadone itself has the potential to increase plasma concentrations of benzodiazepines and increase their sedative effects.
• Several deaths have been reported due to benzodiazepine use in conjunction with high dose buprenorphine and may be a result of similar metabolic interactions.
• Fluvoxamine^xxx, fluoxetine^xx, norfluoxetine^xx and paroxetine^x can inhibit buprenorphine and methadone metabolism through inhibition of the CYPs involved in their metabolism.

10.5.1 Effects of opioids on somatoform disorders

• People with somatoform and pain disorders frequently use opioids. Opioids have analgesic, hypnotic and sedative effects – characteristics that are often sought after or are rewarding for patients with somatoform disorders (particularly pain). There is also evidence that opioids are more likely to be prescribed to people with pain who demonstrate anxiety or depression during an interview^{(417, 418)}.
• Due to the chronic nature of the pain and subsequent opioid use, dependence is common^{(377, 403, 404)}.
• However, long-term opioid use can result not only in tolerance but can actually cause pain hypersensitivity⁽⁴¹⁹⁾, potentially exacerbating somatic symptoms.

10.5.2 Interactions between opioids and therapeutic agents for somatoform disorders

• Opioids, benzodiazepines and antidepressants are metabolised by CYP 450 enzymes which may result in the inhibition or induction of each drug group. Therefore, individuals should be monitored closely to ensure they are receiving the appropriate therapeutic effect and not experiencing increased sedation which may result in impaired driving, injury and, in extreme cases, overdose.
• Combinations of sedative antidepressants such as tricyclics, opioids and benzodiazepines will increase the risk of sedation, overdose, impaired driving and injury.
• Methadone itself has been shown to inhibit CYP3A4^{xx(240, 241)}, which also metabolises many benzodiazepines. This has the potential to increase plasma concentrations of benzodiazepines and increase their sedative effects^{x(242, 243)}.
• Several deaths have been reported due to benzodiazepine use in conjunction with high dose buprenorphine and may be a result of similar metabolic interactions^xxx(244-246).
• Fluvoxamine^xxx, fluoxetine^xx, norfluoxetine^xx and paroxetine^x can inhibit buprenorphine and methadone metabolism through inhibition of the CYPs involved in their metabolism^(148-150). This can result in an increase in plasma opioid pharmacotherapy concentrations and potential overdose. This can be a particular issue during induction onto methadone; however, the risk may persist even after stabilisation has occurred^xxx(151-155).
• Fluvoxamine is the most potent inhibitor of methadone and buprenorphine metabolism and is the most clinically relevant. Therefore, it should be avoided^xxx(150).
• Fluoxetine and paroxetine should also be avoided^xx.
• Citalopram and sertraline are the least likely SSRIs to have cytochrome mediated drug interactions; however, due to the theoretical potential for an interaction, caution should still be used and individuals monitored closely^x(156).

10.5.3 Management approaches to comorbid somatoform disorders and opioid use

• Emphasis should always be placed on non-medication management of the somatoform disorder as a first line of treatment⁽³⁷⁷⁾ when the resources are available and the client is willing to engage.
• CBT has shown reductions in somatic symptoms and improved functioning in people with somatoform disorders^(380-386).
• The risk of dependence should be assessed if opioids are to be used. Risk factors for dependence include⁽⁴²⁰⁾:
  • A personal history of substance dependence.
  • A family history of substance dependence.
  • Age less than 45 years.
  • History of pre-adolescent sexual abuse.
  • Current psychological problems.
• The advice of a specialist pain clinic while optimal, is not always readily available. However, this type of clinic will provide a multi-disciplinary approach to the management of the patient's pain that is not readily available in general practice.
• If opioid dependence is identified, then this needs to be discussed with the patient and their readiness for change identified.
• The patient should be managed with the assistance of a clinical psychologist with experience in the management of pain.
• If exercise and rehabilitation avoidance behaviours are present, then the help of a physiotherapist with experience in the area will be required.
• If opioid analgesics are used, then:
  • Long-acting opioids are preferable.
  • Daily or weekly dispensing of opioids may assist with controlling use (observed single daily dosing may be required).
  • Use of methadone as part of a formalised program will allow probable control of the pain and the drug-seeking lifestyle.
• Use of antidepressants may be required for comorbid depression and anxiety***^{(406, 407)} with tricyclics being useful⁽³⁷⁷⁾, for aiding with chronic tension headaches and fibromyalgia.

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